In this paper, we present a surface plasmon resonance (SPR) based photonic crystal fiber (PCF) sensor for diagnosing deadly malaria. The proposed structure adapts an external sensing scheme that enables the malaria parasite-infected blood sample to be detected easily. We have incorporated dual microchannel in our model to obtain high sensitivity by orienting the plasmonic layer closer to the core region. The flat surface of the microchannel is coated with a silver plasmonic metal and an overlayer of 2D material is coated onto the plasmonic layer. We compare the sensitivity obtained from the 2D MoS2 and graphene layer coating onto the silver layer. We find that MoS2 provides better sensitivity than the uncoated or graphene-coated models. Further, the number of layers of MoS2 has been optimized to be 5 layers of thickness 3.25 nm. After the set of parameters optimization, the proposed sensor exhibits the maximum sensitivities of 7758 nm/RIU, 9210 nm/RIU, and 12,428 nm/RIU, with the maximum spectral resolution of 1.29× 10− 5, 1.09× 10− 5, 8.04× 10− 6 RIU for the schizont, trophozoite, and ring phases, respectively. Besides, we also compute the amplitude sensitivities and they are 354.57, 387.71, and 339.34 RIU− 1 with the maximum amplitude resolution of 8.2× 10− 6,4.9× 10− 6, and 2.06× 10− 6 for the schizont, trophozoite, and ring phases, respectively. Further, we also investigate the other important characteristics of the proposed sensor such as signal-to-noise ratio (SNR), full-width half maximum (FWHM) of the peak, and figure of merit (FOM). In addition to the high sensitivity, the proposed structure also exhibits ultra-low loss for detection. Hence, it can be driven using a low-power source through which the experimental implementation is simplified. Thus, the numerical results corroborate that the proposed sensor is better than existing ones in terms of good sensing performance, cost-effective fabrication, and ultra-low power consumption.